20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells
- 13 October 1998
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (21), 12701-12706
- https://doi.org/10.1073/pnas.95.21.12701
Abstract
Norepinephrine (NE) and angiotensin II (Ang II), by promoting extracellular Ca2+ influx, increase Ca2+/calmodulin-dependent kinase II (CaMKII) activity, leading to activation of mitogen-activated protein kinase (MAPK) and cytosolic phospholipase A(2) (cPLA(2)), resulting in release of arachidonic acid (AA) for prostacyclin synthesis in rabbit vascular smooth muscle cells. However, the mechanism by which CaMKII activates MAPK is unclear. The present study was conducted to determine the contribution of AA and its metabolites as possible mediators of CaMKII-induced MARK activation by NE, Ang II, and epidermal growth factor (EGF) in vascular smooth muscle cells. NE-, Ang II-, and EGF-stimulated MAPK and cPLA(2) were reduced by inhibitors of cytochrome P450 (CYP450) and lipoxygenase but not by cyclooxygenase. NE-, Ang II-, and EGF-induced increases in Ras activity, measured by its translocation to plasma membrane, were abolished by CTP450, lipoxygenase, and farnesyltransferase inhibitors. An AA metabolite of CYP450, 20-hydroxyeicosatetraenoic acid (20-HETE),increased the activities of MAPK and cPLA(2) and caused translocation of Ras. These data suggest that activation of MAPK by NE, Ang II, and EGF is mediated by a signaling mechanism involving 20-HETE, which is generated by stimulation of cPLA(2) by CaMKII. Activation of Ras/MAPK by 20-HETE amplifies cPLA(2) activity and releases additional AA by a positive feedback mechanism. This mechanism of Ras/MAPK activation by 20 HETE may play a central role in the regulation of other cellular signaling molecules involved in cell proliferation and growth.This publication has 50 references indexed in Scilit:
- Protein Kinase C-ζ Mediates Angiotensin II Activation of ERK1/2 in Vascular Smooth Muscle CellsPublished by Elsevier ,1997
- Missing links: Cytochrome P450 arachidonate products: A new class of lipid mediatorsTrends in Cardiovascular Medicine, 1996
- LipoxinsCurrent Opinion in Nephrology and Hypertension, 1996
- 5-Lipoxygenase Products Modulate the Activity of the 85-kDa Phospholipase A2 in Human NeutrophilsJournal of Biological Chemistry, 1995
- Rac mediates growth factor-induced arachidonic acid releaseCell, 1995
- Ras-dependent activation of MAP kinase pathway mediated by G-protein βγ subunitsNature, 1994
- Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1Nature, 1993
- Activation of the MAP kinase pathway by the protein kinase rafCell, 1992
- The newly synthesized selective Ca2+calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cellsBiochemical and Biophysical Research Communications, 1991
- Selective inhibition of platelet lipoxygenase by baicaleinBiochemical and Biophysical Research Communications, 1982